Ji-Fang
Zhang, PhD

Medical School

PhD, in Pharmacology, Columbia University - 1991

Expertise and Research Interests

My lab is interested in voltage-gated Ca2+ channels (VGCCs) and Ca2+ influx in neuronal signaling, in particular, how Ca2+ influx through different types Ca2+ channels is able to specifically initiate/regulate different signaling pathways. We have focused on identification and functional characterization of novel Ca2+ channel partner proteins and their roles in Ca2+-dependent signaling in neurons. These novel Ca2+ channel partner proteins were identified by yeast two-hybrid screening using the C-termini of three different types of VGCCs. biochemical and functional characterization of these novel Ca2+ channel partner proteins are in progress using combined approaches of molecular biology, biochemistry, cell biology, electrophysiology and fluorescence imaging. In particular, we are focusing on the following areas:

(1) Ca2+ channels and Ca2+ influx in regulating synaptic vesicle recycling. We will continue to address the role of Ca2+ channels and Ca2+ influx in vesicular endocytosis. (a) Identifying all amino acid residues which form the Ca2+ sensor; (b) examining the enzymatic activities of endophilin at different Ca2+ levels; and (c) examining the effects of dominant negative constructs on hippocampal neurons to see how Ca2+ regulates vesicle endocytosis. (d) solving the crystal structures of the novel Ca2+ sensor. In addition to endophilin, we have identified several other proteins which are implicated in synaptic vesicle recycling.

(2) Roles of motor protein subunits in determining sorting and trafficking of different types of Ca2+ channels. We will continue to examine interactions between motor proteins and Ca2+ channels; particularly focusing on (a) how such interactions can be regulated, e.g. phosphorylation, (b) how such interactions may contribute to synaptogenesis; and (c) potential roles of these interactions in synaptic plasticity.

(3) The unique roles of Ca2+ channels and Ca2+ influx in regulation of gene expression, particularly in synaptic plasticity and in certain forms of neurodegeneration. We will focus on several proteins we identified during yeast two-hybrid screening. These proteins are known to be involved in regulation of gene expression. We will test whether interactions of these proteins with Ca2+ channels contribute to activity-dependent regulation of gene expression in neurons. Mutations in P/Q-type Ca2+ channels, particularly in the channel C-terminus, have been implicated in neurodegeneration, as well as diseases such as certain forms of epilepsy, migraines and ataxia. Defects in P/Q-type Ca2+ channels cannot be compensated by other types of Ca2+ channels. We want to test the hypothesis that P/Q type Ca2+ channel mutations alter the Ca2+-dependent signaling process and consequently lead to neurodegeneration.

(4) Modulation of Ca2+ channel activities though specific signaling complex. We will continue to examine the dynamics of the PKC signaling complex, and how formation of this complex is regulated by physiological factors; particularly (a) effects of phosphorylation by PKC on the formation of the complex; and (b) how phosphatase fits into complex.

The research activities in my lab are currently supported by grants from NIMH and NINDS of the National Institutes of Health.